Beneficial health effects of certain fat soluble nutrients, such as, vitamins A, D, E and K, carotenoids, glycerides, fatty acids such as saturated and monounsaturated acids, capsaicin, Co-enzyme Q-10, Ubiquinol as well as curcumin are well known. These nutrients form an important part of the human diet. However, being lipophilic in nature, these nutrients are insoluble in water and pose serious absorption constraints with variable bioavailability profile. Hence development of compositions containing such nutrients is one of the most important areas which are being explored to a great extent.
Carotenoids are a family of yellow to orange-red terpenoid pigments synthesized by photosynthetic organisms and by many bacteria and fungi. They offer protection against oxidative damage and are responsible for the appearance of these colours in plants and animals. Carotenoids are also desirable commercial products used as additives and colorants in the food industry. Traditionally, carotenoids were obtained by extraction from plants or by direct chemical synthesis. They may be linear or have undergone ring closure at one or both ends. The ring structure(s) may carry hydroxy or keto groups. In all cases, the molecules are predominantly hydrophobic and are usually found in lipid domains of plant and animal tissues. Of the wide range of animal and vegetable foods that comprise the human diet, most contribute at least trace amounts of some of the 600 identified carotenoids and related compounds. However, only a few carotenoids from fruits and vegetables, are ingested in sufficient quantity to be detected in human plasma, the most abundant being beta-carotene, lutein, lycopene, alpha-carotene, beta-cryptoxanthin and zeaxanthin, along with their more common cis-isomers and some degradation products. Hence it is important to develop the formulations which would exhibit enhanced solubility and thus result in increased absorption in body fluids, to satisfy a daily requirement. Stability of these nutrients is also a concern due to their inherent chemical structure which is prone to oxidative and photogenic degradation; hence many efforts are also oriented towards getting stable formulations with robust processing steps which minimize the degradation.
Prior art references deal with numerous methods for preparing microencapsulated or coated compositions of fat soluble nutrients employing suitable excipients in order to increase stability and solubility.
U.S. Pat. No. 7,045,643 relates to a method for preparation of stable microcrystalline lutein formulations which involves dissolution of lutein in organic solvent in presence of antioxidants and vegetable oils, emulsifying and microencapsulating the organic solution with aqueous solution of modified starch using homogenization and evaporating until microcrystallization of lutein occurs. Modified starch such as octenyl succinate which is derived from waxy maize is used here to encapsulate lutein microcrystals. However such hydrophobically modified polymer and vegetable oil used in process of encapsulation may result in lower solubility of lutein microcrystals in body fluids, also the process for microencapsulation is costly and results in variable rate of active release from the formulation.
U.S. Pat. No. 3,998,753 demonstrates solubilization of carotenoids by preparing solutions of carotenoids in volatile organic solvents, such as halogenated hydrocarbons, and further emulsifying them with an aqueous solution of sodium lauryl sulphate in the presence of gelatine as the matrix.
U.S. Pat. No. 4,670,247 discloses the preparation of fat soluble beadlets by emulsifying a fat soluble active such as a vitamin, flavoring or aromatic substances with water, gelatin and a reducing sugar. The emulsion is then converted to droplets. The droplets are collected in a starch powder to form particles which are heat treated to form a water insoluble beadlet.
A gelatin matrix as used in the above prior art document results in beadlets which are water insoluble and hence may result in lower solubility of the active nutrient, thus affecting bioavailability.
However, polymers derived from animals may not be preferred in nutritional products; due to for example challenging acceptability by users and customers.
U.S. Pat. No. 6,146,671 discloses a method for a heat and/or oxygen-labile compound by encapsulation in a protective matrix of alginate and an additional polymeric material like gelatin, which provides a single layer coating system.
U.S. Pat. No. 7,097,868 relates to microencapsulated beadlet composition prepared by adding sodium/potassium alginate as an encapsulating polymer to a solution of lipophilic compound in the presence of a surface active agent and obtaining beadlets with improved stability. Even though sodium/potassium alginate may aid increased stability, its viscosity is at least 10 centipoise (cP) of 1% solution in water, further its concentration used in this invention (about 8 times of lipophilic compound) is very high which may lead to lag time for release of the active nutrient from such beadlet formulation. Further such systems may not be robust with respect to in vitro-in vivo co-relation because of a viscous matrix formed through which the active nutrient has to diffuse out for release in gastrointestinal tract (GIT), thus affecting subsequent absorption of the active nutrient, e.g. fat soluble nutrient.
U.S. Pat. No. 8,680,161 teaches compositions containing plant gums such as gum Arabic, gum Ghatti, at least one modified starch and one or more fat-soluble active ingredients, wherein the composition comprises less than 40 weight % oil. These compositions need a third coating layer for stability of beadlets. Particle size reduction of lipophilic compound was carried out in the presence of a surfactant which resulted in enhanced stability. However, a size reduction of lipophilic compounds may tend to agglomeration of the active and may also lead to increased cost making it resource sensitive.
U.S. Pat. No. 8,597,642 describes a multivitamin tablet formulation comprising a protective colloid of a modified starch like sodium octenyl succinate with maltodextrin, carbohydrates or gums along with an emulsifier.
Modified starches are made from starches substituted by known chemical methods with hydrophobic moieties. For example, starch may be treated with cyclic dicarboxylic acid anhydrides such as succinic anhydrides and substituted with a hydrocarbon chain.
The reference aims at use of hydrophobically modified starch derivatives for increasing absorption of fat soluble actives, which is not a desirable option as it may add further to the lipophilic property of the active ingredient, rendering it less soluble in a biological system.
U.S. Pat. No. 8,211,471 describes a process for the production of cross-linked beadlets wherein an emulsion of a carotenoid and vitamin A, polyunsaturated fatty acid, an emulsifier and a reducing sugar is prepared and converted to droplets, where these droplets are coated with finely dispersed calcium silicate powder. These beadlets are characterized by high stability and potency. However, these cross-linked beadlets are water insoluble and hence have limited bioavailability.
U.S. Pat. No. 7,691,297 relates to a process for the manufacture of beadlet preparations of fat-soluble substances in a water-soluble or water-dispersible non-gelling sulfonated lignin matrix along with corn starch wherein an aqueous emulsion of the fat-soluble substance(s) and the matrix component are fed through a spray nozzle. In recent years, the rheological properties of the sulfonated lignin especially at the lower pH, has become an area of concern. This negative viscosity behaviour of sulfonated lignins may need to be tackled in such systems to get robust composition with desired solubility profile.
European Patent EP1212071B1 describes beadlets comprising xanthophylls and carotenes and/or retinoids, as well as dietary supplements comprising these beadlets and their methods of use. The particles of xanthophylls are embedded in a highly viscous gelatin-sucrose matrix. Upon oral administration of the developed formulation, the xanthophylls get released in the gastro-intestinal-tract from these formulations, in a slow and erratic fashion due to lower solubility and consequently the bioavailability of the composition is significantly reduced.
Patent application WO2009022034A1 describes manufacturing carotenoid compositions by dissolving a carotenoid in an organic solvent, emulsifying the resulting solution into an aqueous solution of a protective colloid and subsequently removing the solvent from this emulsion. The disadvantage of this process is the use of chlorinated hydrocarbons as the solvent for the active nutrient and its subsequent removal which is an environmental burden, thus making the process extremely expensive from a commercial point of view.
European patent application EP2696704A1 teaches a process for the manufacture of a lutein powder formulation comprising the steps of providing an aqueous solution/suspension of a polysaccharide; adding lutein in a modified polysaccharide solution/suspension and milling the suspension followed by drying the suspension. These modified polysaccharides such as glucose (syrup) and modified food starch contain a lipophilic moiety, e.g. a hydrocarbon moiety having a chain length of preferably 5 to 18 carbon atoms in the straight chain.
The formulations either aim at increasing stability by using a combination of antioxidants and emulsifier or at increasing solubility by employing encapsulating polymers such as reducing sugars, gelatin, sodium alginate, polysaccharide or modified starch derivatives. Particle size reduction is also carried out by grinding with a surfactant, thus focusing on increased solubility. These polymeric systems employ polymers which are either hydrophobic in nature or have considerable/higher viscosity at the concentrations used in the composition, thus affecting the resultant solubility.
Hence there is a need for alternative and improved stable beadlet formulations of fat soluble nutrients with an enhanced solubility and bioavailability profile. Such formulations should demonstrate good in vitro-in vivo co-relation, thus minimizing variable inter-personal absorption profiles.